pathogenesis of liver disease in hepatitis
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Publication
Journal: Journal of Experimental Medicine
January/14/1992
Abstract
The absence of readily manipulable experimental systems to study the cytotoxic T lymphocyte (CTL) response against hepatitis B virus (HBV) antigens has thus far precluded a definitive demonstration of the role played by this response in the pathogenesis of liver cell injury and viral clearance during HBV infection. To circumvent the problem that HBV infection of human cells in vitro for production of stimulator/target systems for CTL analysis is not feasible, a panel of 22 overlapping synthetic peptides covering the entire amino acid sequence of the HBV core (HBcAg) and e (HBeAg) antigens were used to induce and to analyze the HBV nucleocapsid-specific CTL response in nine patients with acute hepatitis B, six patients with chronic active hepatitis B, and eight normal controls. By using this approach, we have identified an HLA-A2-restricted CTL epitope, located within the NH2-terminal region of the HBV core molecule, which is shared with the e antigen and is readily recognized by peripheral blood mononuclear cells from patients with self-limited acute hepatitis B but less efficiently in chronic HBV infection. Our study provides the first direct evidence of HLA class I-restricted T cell cytotoxicity against HBV in humans. Furthermore, the different response in HBV-infected subjects who successfully clear the virus (acute patients) in comparison with patients who do not succeed (chronic patients) suggests a pathogenetic role for this CTL activity in the clearance of HBV infection.
Publication
Journal: Molecular biology & medicine
March/8/1990
Abstract
In order to study aspects of the biology and pathogenesis of the hepatitis B virus (HBV), not readily approachable by existing tissue culture systems and animal models, several groups have introduced the HBV genome and subgenomic fragments into the germ line of transgenic mice. Substantial new information has been forthcoming from these studies in several areas including tissue-specific expression, hormonal regulation, sex influences, viral replication and disease pathogenesis. These developments are reviewed in the context of the genetic organization and functional properties of the virus and its gene products, and their implications with respect to HBV biology and pathogenesis are discussed.